1 IPEC-Americas General Information Go to for additional informationwww.ipecamericas.org OR contact info to or Kim Beals

2 IPEC Executive Committee Chair – David Klug (Sanofi US) Past Chair – Dale Carter (J.M. Huber, Engineered Materials) Chair Elect - John Giannone (Noramco Inc. via J&J) VC Administrative Affairs – Janeen Skutnik-Wilkinson (NSF DBA) VC Harmonization & Compendia Monographs -Priscilla Zawislak (Ashland Inc.) VC Membership – Nigel Langley (BASF) VC Science & Regulatory Affairs – Katherine Ulman (DowCorning) VC User Relations - Tom Schultz (J&J) VC Maker/Distributor Relations – David Schoneker (Colorcon) XC at Large - Bretta Lichtenhan (EMD Millipore) XC at Large - Gina Marsee (Pfizer Inc.) XC at Large – Linda Mikulan-Maxfield (Baxter) XC at Large - Ann Van Meter (Dow Woulf Cellulosics)

333 IPEC: Where Industry Standards are Defined by The Excipient Experts IPEC-Americas is a non-profit trade association with many diverse member companies –Excipient development –Excipient manufacturing and distribution –Pharma companies that use excipients Is your company an IPEC member? This is a subset of the 62 companies that are members of IPEC-Americas

444 IPEC BACKGROUND Founded in 1991 as a Non-Profit Association of Pharmaceutical Manufacturers, Excipient Manufacturers and Distributors Develop, implement and promote voluntary, science and risk-based guidance for excipients Assist and cooperate globally with regulatory authorities, industry organizations and scientific bodies working to advance public health on matters relating to the manufacture, distribution, use, and functionality of excipients.

55 IPEC History & Guidance Documents EQ 1 IPEC/PQG Audit IPEC Forms Reg. Affairs Confer. combines with Excipient Fest Reg. Affairs Conf. Reg. Affairs Conf. Reg. Affairs Conf. Excipient GMP USP Safety Evaluation of New Excipient USP GMP Audit GMP Audit Distributors Cert. of Analysis USP GMP Rev1 EMF GMP Audit Rev Sig. Change USP EIP GDP IPEC/PQG GMP EQ 1, 2, 3 Pedigree Paper Sig Change R1 EIP Template Quality Agree. Stability Composition

666 Why IPEC-Americas? Because there is No Real Pharmaceutical Excipient Industry Majority of Pharmaceutical Excipient Suppliers are Chemical Industry subsidiaries Products targeted at Food, Beverage, Industrial, and Cosmetic Small fraction of Main Production Volumes for excipient Varying degrees of dedicated R&D related to excipient uses Specifications-driven by main market (usually not Pharma) Global Market and Manufacturing Base

777 What is the Excipient Industry? Diverse Materials Base Chemical synthesis (Polymer mixtures, Cellulose derivatives – substances often less defined than low mol wt entities) Mining of minerals Harvesting of vegetation Formulated Products Biotechnology & Fermentation Genetic Modification Animal by-products

8 What excipient users and makers share The maker’s packing area is the start of user’s processing area They maker’s storage area is the users ingredient storage area The maker’s finish product testing lab is the user’s incoming ingredient testing lab The reliability of the maker’s product is the reliability of the user’s drug product supply The maker’s declaration of stability for the excipient is the users information source for the stability of the excipient

IPEC-Americas Provides Balance Maker members covering the diversity of excipients Distributor members User members 9 This combination of members provides the full view of issues surrounding excipients, providing IPEC-Americas the unique capability to develop science based guidance and position documents that work.

10 Starting point of an excipient qualification program –IPEC Excipient Qualification Guide –IPEC Excipient Composition Guide Ask your supplier and follow the chain to the manufacturer –IPEC-Americas Standardized Excipient Information Protocol –Excipient Pedigree White Paper Know the history and reputation of each party Understand the practices followed at each step –IPEC-PQG GMP Guide for Pharmaceutical Excipients –IPEC Good Distribution Practices Guide –IPEC-Americas Significant Change Guide –IPEC-Americas Certificate of Analysis Guide –IPEC Stability Guide Match risk and controls –IPEC Standardized Quality Agreement Template IPEC Guides and the Excipient Supply Chain

11 The Joint IPEC – PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients 2006 Connects the expectations of excipient users with terminology and practices of excipient manufactures so that the underlying GMP principles may be understood and implemented.

12 The Joint IPEC-PQG Good Manufacturing Practices Guide for Pharmaceutical Excipients 2006 Basic Quality Management Systems principles plus key processes necessary to ensure production of safe consistent products Emphasizes communication between manufacture and user –Significant Change –Certificate of Analysis –Stability International in scope Useful and acceptable to Suppliers, Users and regulators

13 GMP Goal is to Manage Risk GMP Goal is to Manage Risk Risk to Drug Maker & Risk to Patient Adulteratedexcipient causes failure of drug batch during manufacturing Adulteratedexcipient causes failure of drug in use or results in hazardous product 21 CFR (a)(9) 21 CFR 330.1(e)

14 Qualification provides information for Supply Chain Controls Excipient Pedigree  Do you know where your ingredients are produced?  Do you know how they were distributed?  What evidence do you have which demonstrates this?  More than One Up and One Down in supply chain is needed! What is your weakest link…………..?

Evaluating Excipient Manufacturers QUALIFICATION OF EXCIPIENTS FOR USE IN PHARMACEUTICALS Covers all aspects of Excipient Qualification Includes both the User’s and Maker’s perspective Designed to improve communication and understanding between makers and users References other IPEC Guides

Evaluating Excipient Manufacturers QUALIFICATION OF EXCIPIENTS FOR USE IN PHARMACEUTICALS Phase 1 -Excipient development and market launch by excipient manufacturers Phase 2 - Excipient selection and overall qualification for intended use by excipient users Phase 3 - Negotiation of mutually acceptable specifications and quality agreements

17 Phase 1: Excipient Supplier’s Process Section 2: General Guidance –Differentiation of Excipient Manufacture –Preliminary Marketing Decision & Regulatory Assessment –Manufacture and Packaging Section 3: Excipient Development and Specification Process –Excipient Consistency and Control, Performance Indicators –Production Specifications and Master Batch Record –Marketing Materials, Customer Feedback, Post Launch –Confidentiality

18 Phase 2: The User’s Process Section 4: Assessment, Selection and Specification Process –Project initiation –New Formulation Development Selecting the Excipients Selecting the Supplier Regulatory Assessment Refining the Excipient list Formulation Design, Development and Optimization –Alternate Excipient Sourcing

19 Phase 3: The Negotiation Process Section 5: Negotiating the Supply –Review of User Requirements –Quality Agreements –Modification of Requirements –Potential solutions Lot selection Manufacture to order –Other approaches In-house processing Reformulation Custom manufacture

20 IPEC Guidelines = Consistency in Excipient Practices Significant Change Guide Excipient Information Package Quality Agreements Excipient Stability Certificate of Analysis (under revision) One thing is clear from past experience – Everyone developing their own solution independently serves no one